ALCOHOLISM: CLINICAL AND EXPERIMENTAL RESEARCH

Vol. 39, No. 8 August 2015

Critical Review

Moderate Alcohol Consumption and Colorectal Cancer Risk DawnKylee S. Klarich, Susan M. Brasser, and Mee Young Hong

Background: Heavy alcohol drinking is a risk factor for colorectal cancer (CRC); previous studies have shown a linear dose-dependent association between alcohol intake and CRC. However, some studies suggest that moderate alcohol consumption may have a protective effect, similar to that seen in cardiovascular disease. Other factors may interact with alcohol and contribute additional risk for CRC. We aimed to determine the association between moderate alcohol consumption, limited to 30 g of alcohol per day, by beverage type on CRC risk and to assess the effects of other factors that interact with alcohol to influence CRC risk. Methods: The PubMed database was used to find articles published between 2008 and 2014 related to alcohol and CRC. Twenty-one relevant articles were evaluated and summarized, including 11 articles reporting on CRC risk associated with moderate intake and 10 articles focusing on genetic interactions associated with alcohol and CRC risk. Results: The association between alcohol and increased risk for CRC was found when intakes exceeded 30 g/d alcohol. Nonsignificant results were consistently reported for intakes 8 g/ d alcohol, HR 0.61 (95% CI 0.40 to 0.94, p = 0.04), and a near significant reduced risk for rectal cancer, HR 0.28 (95% CI 0.10 to 0.80, p = 0.06) (Park et al., 2009). Effects for High Alcohol Intake One study from the Netherlands reported a statistically significant increase in rectal cancer risk for alcohol intake ≥30 g/d with a HR of 1.50 (95% CI 1.05 to 2.16, p not reported) (Bongaerts et al., 2008). The risk of CRC was increased in Finnish men consuming the highest quintile of alcohol, which ranged from 16.5 to 407 g/d, with a RR of 3.5 (95% CI 1.2 to 9.8, p = 0.02) (Toriola et al., 2008). There was a significant increase in risk for those consuming >48 g/ d of alcohol in a Mediterranean population, OR 3.41 (95% CI 1.55 to 7.48, p < 0.003) (Kontou et al., 2012). Similar reports from a different Mediterranean population study found significantly increased risk for colon cancer and rectal cancer at intakes above 48 g/d, OR 1.86 (95% CI 1.01 to 3.45, p = 0.048) and 2.29 (95% CI 1.14 to 4.58, p = 0.020),

KLARICH ET AL.

1286

Table 2. (Continued) Study type, population

Measurement type

Results

Conclusion

Slattery and colleagues (2010)

Author (year)

Case–control, U.S. 1997 to 2001 Cases: 750 rectal cancer Controls: 829 Baseline 30 to 79 years old

Assessment of tumor markers associated with frequent alterations in colorectal tumors: CIMP, TP53 mutations, and KRAS2 mutations with regard to CRC risk in relation to alcohol

High beer consumption significantly increased the risk of having a TP53 tumor mutation, while red wine was nonsignificantly inversely associated with a TP53 mutation. Independent of genetic risk factors, total alcohol intake was not significantly associated with increased risk for rectal cancer

Yin and colleagues (2012)

Case–control, Japan 2000 to 2003 (FCCS) Cases: 658 Controls: 778 Baseline 20 to 74 years old

XRCC1 gene, responsible for DNA repair, SNPs: Arg194Trp, Arg280His, Arg399Gln and their effects on CRC risk in relation to alcohol

Statistically significant association between high beer intake and TP53 rectal mutation OR: 1.97 (1.24 to 3.12) p = 0.02 No statistically significant association OR for all cases rectal cancer: Moderate 1.03 (0.83 to 1.28) High 0.92 (0.72 to 1.16) p = 0.56 Statistically significant interaction for Arg280His OR for CRC: Arg/Arg: 30 g/d was no longer sta-

tistically significant at 1.13 (95% CI 0.85 to 1.51) (Nan et al., 2013). Obesity Status. When body mass index (BMI) was included as a risk factor for the development of CRC, significant differences were observed between alcohol intake levels and the risk of CRC (Zhao et al., 2012). Individuals who consumed 13.5 to 27 g/d alcohol and were not obese, with a BMI 30 g/d alcohol

MODERATE ALCOHOL INTAKE AND COLON CANCER

Morita M, Le Marchand L, Kono Yin G, Toyomura K, Nagano J, Mizoue T, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Maekawa T, Yasunami Y, Takenaka K, Ichimiya H, Imaizumi N (2009) Genetic polymorphisms of CYP2E1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study. Cancer Epidemiol Biomarkers Prev 18:235–241. Mukamal KJ, Conigrave KM, Mittleman MA, Camargo CA, Stampfer MJ, Willett WC, Rimm EB (2003) Roles of drinking pattern and type of alcohol consumed in coronary heart disease in men. N Engl J Med 348:109– 118. Nan H, Lee JE, Rimm EB, Fuchs CS, Giovannucci EL, Cho E (2013) Prospective study of alcohol consumption and the risk of colorectal cancer before and after folic acid fortification in the United States. Ann Epidemiol 23:558–563. Park JY, Dahm CC, Keogh RH, Mitrou PN, Cairns BJ, Greenwood DC, Spencer EA, Fentiman IS, Shipley MJ, Brunner EJ, Cade JE, Burley VJ, Mishra GD, Kuh D, Stephen AM, White IR, Luben RN, Mulligan AA, Khaw KT, Rodwell SA (2010) Alcohol intake and risk of colorectal cancer: results from the UK Dietary Cohort Consortium. Br J Cancer 103:747–756. Park JY, Mitrou PN, Dahm CC, Luben RN, Wareham NJ, Khaw KT, Rodwell SA (2009) Baseline alcohol consumption, type of alcoholic beverage and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition-Norfolk study. Cancer Epidemiol 33:347–354. Pedersen A, Johansen C, Gronbaek M (2003) Relations between amount and type of alcohol and colon and rectal cancer in a Danish population based cohort study. Gut 52:861–867. Poynter JN, Haile RW, Siegmund KD, Campbell PT, Figueiredo JC, Limburg P, Young J, Le Marchand L, Potter JD, Cotterchio M, Casey G, Hopper JL, Jenkins MA, Thibodeau SN, Newcomb PA, Baron JA (2009) Associations between smoking, alcohol consumption and colorectal cancer, overall and by tumor microsatellite instability status. Cancer Epidemiol Biomarkers Prev 18:1–14.

1291

Razzak AA, Oxentenki AS, Vierkant RA, Tillmans LS, Wang AH, Weisenberger DJ, Laird PW, Lynch CF, Anderson KE, French AJ, Haile RW, Harnack LJ, Slager SL, Smyrk TC, Thibodeau SN, Cerhan JR, Limburg PJ (2011) Alcohol intake and colorectal cancer risk by molecularly-defined subtypes in a prospective study of older women. Cancer Prev Res 4:2035– 2043. Seitz HK, Stickel F (2010) Acetaldehyde as an underestimated risk factor for cancer development: role of genetics in ethanol metabolism. Genes Nutr 5:121–128. Slattery ML, Wolff RK, Herrick JS, Curtin K, Caan BJ, Samowitz W (2010) Alcohol consumption and rectal tumor mutations and epigenetic changes. Dis Colon Rectum 53:1182–1189. Solomon CG, Hu FB, Stampfer MJ, Colditz GA, Speizer FE, Rimm EB, Willett WC, Manson JE (2000) Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus. Circulation 102:494–499. Toriola AT, Kuri S, Laukanen JA, Mazengo C, Kauhanen J (2008) Alcohol consumption and risk of colorectal cancer: the Findrink study. Eur J Epidemiol 23:395–401. World Cancer Research Fund/American Institute for Cancer Research (2007) Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Prospective. World Cancer Research Fund/American Institute for Cancer Research, Washington, DC. Yin G, Morita M, Ohnaka K, Toyomura K, Hamajima N, Mizoue T, Ueki T, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya H, Terasaka R (2012) Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan. J Epidemiol 22:64–71. Zhao J, Zhu Y, Wang PP, West R, Buehler S, Sun Z, Squires J, Roebothan B, McLaughlin JR, Campbell PT, Parfrey PS (2012) Interaction between alcohol drinking and obesity in relation to colorectal cancer risk: a case– control study in Newfoundland and Labrador, Canada. BMC Public Health 12:1–9.

KLARICH ET AL.

1284

Table 2. Characteristics of Published Cohort and Case–Control Studies on Genetic Risk Factors Associated with Alcohol Intake and CRC Risk Author (year)

Study type, population

Measurement type

Bongaerts and colleagues (2011)

Case–control, Netherlands 1986 to 1993 (NLCS) Cases: 594 Controls: 1,649 Baseline 55 to 69 years old

Determine effect of ADH1C functional SNP, homozygous ADH1C*1 2.59 faster enzyme rate than homozygous ADH1C*2 at metabolizing alcohol, on CRC risk

Cho and colleagues (2012)

Cohort, U.S. 1980 to 2008 87,861 women (NHS) Baseline 30 to 55 years old 1986 to 2008 47,290 men (HPFS) Baseline 40 to 75 years old

Determine association of family history of CRC with regard to its role in genetic susceptibility to the development of CRC in relation to alcohol intake

Ferrari and colleagues (2012)

Case–control, Europe 1992 to 1998 (EPIC) Cases: 1,269 Controls: 2,107 Mean age: 58  7 years

Determine association between ADH1B, ADH7, and ALDH2 gene polymorphism with CRC risk in relation to alcohol intake

Gao and colleagues (2008)

Case–control, China 2000 to 2002 Cases: 190 Controls: 223

Determine association between ADH2 and ALDH2 gene polymorphism with CRC risk in relation to alcohol intake

Results No statistically significant risk for CRC with genotype and alcohol intake RR: ADH1C*1/*1 25 and >50 g/d women and men, respectively) and genotype on OR for CRC: ADH7 G/C or C/C (variant) 2.13 (1.26 to 3.59) p = 0.04 ALDH2 T/T (wild type) 1.43 (1.06 to 1.94) p = 0.03 ADH2 A/A (variant) faster alcohol metabolizer OR for CRC: 1.60 (1.08 to 2.36) p not reported ALDH2 G/G (wildtype) active acetaldehyde metabolizer OR for CRC: 1.79 (1.19 to 2.69) p not reported Alcohol consumption (g/mo) OR for CRC: 300 to 599 (1 to 2 D/d) 1.98 (0.96 to 4.09) ≥600 (>2 D/d) 2.33 (1.47 to 3.71) p = 0.0001

Conclusion Consumers of ≥30 g/d of alcohol with either genetic variant of ADH1C were positively, but not statistically significantly, associated with the risk of CRC

Results imply that variation in certain inherited factors involved in the metabolism of alcohol may partly contribute to the genetic susceptibility that correlates higher alcohol intakes with elevated CRC risk Evidence suggested that ADH1B polymorphisms, associated with the fast alcohol metabolizer allele, were associated with a reduction in alcohol intake. The relationship between high alcohol intake and risk of CRC was modulated by the interaction of the ADH7 polymorphism ADH2 and ALDH2 genotypes were moderately associated with increased risk of developing CRC in Chinese males. Significant genealcohol interaction was observed with the slower alcohol metabolizing variants having less CRC risk associated when consuming alcohol. Variant ALDH2 genotypes resulted in lower risks for CRC

Continued.

MODERATE ALCOHOL INTAKE AND COLON CANCER

1285

Table 2. (Continued) Measurement type

Results

Conclusion

Gao and colleagues (2013)

Author (year)

Case–control, China 2000 to 2003 Cases: 190 men, 125 women Controls: 223 men, 216 women

Study type, population

XRCC1 gene, responsible for DNA repair, SNPs: Arg194Trp, Arg399Gln and their effects on CRC risk in relation to alcohol

The results suggest that XRCC1 polymorphisms themselves have no biological impact on CRC risk, while an interaction with high intakes of alcohol is plausible. 194 Trp allele or 399 Gln allele and high intake showed nonsignificant positive trends for increasing CRC risk

Homann and colleagues (2009)

Case–control, Germany 2000 to 2005 Cases: 173 patients with colorectal polyps Controls: 788

Determine association between ADH1C gene polymorphism and tumor risk in the colon at high alcohol intake

Statistically significant association between high alcohol intake and CRC for Total Sample Population OR: 1 to 20 g/d 1.35 (0.81 to 2.20) >20 g/d 2.38 (1.51 to 3.74) p < 0.0001 No statistically significant interaction for SNP and high intake OR for CRC: >20 g/d Arg194Trp Arg/Arg 2.40 (1.26 to 4.57) Arg/Trp + Trp/Trp 3.18 (1.68 to 5.99) >20 g/d Arg399Gln Arg/Arg 1.93 (1.00 to 3.70) Arg/Gln + Gln/Gln 2.17 (1.13 to 4.17) p not reported Patients with alcoholrelated colorectal tumors had a significantly higher ADH1C*1 allele frequency of 61.8% as compared to controls (50.0%) p not reported

Morita and colleagues (2009)

Case–control, Japan 2000 to 2003 (FCCS) Cases: 685 Controls: 778 Baseline 20 to 74 years old

Determine association of CYP2E1 RsaI and 96-bp insertion polymorphism with CRC risk in relation to alcohol

Poynter and colleagues (2009)

Case–control, U.S., Canada, Australia, (Colon CFR) 1998 to 2005 Cases: 2,253 Controls (siblings): 4,486

Evaluate the association between alcohol consumption and CRC by tumor MSI status

Statistically significant association between ≥2 D/d and genetic variant OR for CRC: RsaI c1/c1 1.56 (1.05 to 2.43) p = 0.03 c1/c2-c2/c2 1.29 (0.79 to 2.11) p = 0.40 96-bp 0 insertion 1.78 (1.19 to 2.68) p = 0.009 96-bp 1 to 2 insertions 0.98 (0.59 to 1.62) p = 0.88 Statistically significant association between >12 D/wk and rectal cancer in men OR: 1.60 (0.95 to 2.68) p = 0.03 Alcohol was associated with MSI-L CRC OR for >12 D/wk: 1.85 (1.06 to 3.24) p = 0.03

Subjects with a high alcohol intake (>30 g/d) and who were homozygous for ADH1C*1/*1 were at a higher risk of developing CRC. Data provided additional evidence of acetaldehyde accumulation contributing carcinogenic effects in CRC development Suggested that genetic variability in metabolic activity and inducibility of CYP2E1, in relation to high alcohol intake, may contribute to the development of CRC

The highest intake of alcohol was associated with a modest increased risk of rectal cancer in males and was also significantly associated with MSI-L CRC in both males and females. Results represent the potential for incorporating tumor characteristics in studies identifying risk factors for CRC

Continued.

KLARICH ET AL.

1286

Table 2. (Continued) Study type, population

Measurement type

Results

Conclusion

Slattery and colleagues (2010)

Author (year)

Case–control, U.S. 1997 to 2001 Cases: 750 rectal cancer Controls: 829 Baseline 30 to 79 years old

Assessment of tumor markers associated with frequent alterations in colorectal tumors: CIMP, TP53 mutations, and KRAS2 mutations with regard to CRC risk in relation to alcohol

High beer consumption significantly increased the risk of having a TP53 tumor mutation, while red wine was nonsignificantly inversely associated with a TP53 mutation. Independent of genetic risk factors, total alcohol intake was not significantly associated with increased risk for rectal cancer

Yin and colleagues (2012)

Case–control, Japan 2000 to 2003 (FCCS) Cases: 658 Controls: 778 Baseline 20 to 74 years old

XRCC1 gene, responsible for DNA repair, SNPs: Arg194Trp, Arg280His, Arg399Gln and their effects on CRC risk in relation to alcohol

Statistically significant association between high beer intake and TP53 rectal mutation OR: 1.97 (1.24 to 3.12) p = 0.02 No statistically significant association OR for all cases rectal cancer: Moderate 1.03 (0.83 to 1.28) High 0.92 (0.72 to 1.16) p = 0.56 Statistically significant interaction for Arg280His OR for CRC: Arg/Arg: 30 g/d was no longer sta-

tistically significant at 1.13 (95% CI 0.85 to 1.51) (Nan et al., 2013). Obesity Status. When body mass index (BMI) was included as a risk factor for the development of CRC, significant differences were observed between alcohol intake levels and the risk of CRC (Zhao et al., 2012). Individuals who consumed 13.5 to 27 g/d alcohol and were not obese, with a BMI 30 g/d alcohol

MODERATE ALCOHOL INTAKE AND COLON CANCER

intake and CRC in men with a family history of CRC, RR 2.01 (95% CI 1.06 to 3.70, p = 0.009) (Cho et al., 2012). The risk no longer reached a level of significance for men consuming the same level of alcohol, but with no family history of CRC, RR 1.30 (95% CI 0.95 to 1.79, p = 0.08) (Cho et al., 2012). The results were further stratified to determine the association by folate intake, in which abstainers with no family history of CRC and a folate intake greater or equal to 300 lg/d were used as the reference group (Cho et al., 2012). The pooled multivariate RR for colon cancer was 2.09 (95% CI 1.28 to 3.39) for individuals with a family history of CRC who drank >30 g/d and had a folate intake greater or equal to 300 lg/d, but was elevated when folate was below 300 lg/d, RR 3.59 (95% CI 2.30 to 5.62) (Cho et al., 2012). ADH and ALDH Polymorphism. Individuals from a Chinese population with ADH2 A/A variant metabolized alcohol at a faster rate than G/G wild type and had higher associated risk for CRC, independent of alcohol quantity, with an OR of 1.60 (95% CI 1.08 to 2.36, p not reported) (Gao et al., 2008). The risk increased to 3.44 (95% CI 1.84 to 6.42, p not reported) when the interaction of alcohol was evaluated (Gao et al., 2008). In a population from the Netherlands, ADH1C genotypes were found to have a functional polymorphism in which ADH1C*1/*1 carriers metabolize alcohol approximately 2.5 times faster than ADH1C*2/*2 carriers (Bongaerts et al., 2011). For alcohol intakes below and above 30 g/d, the risk for CRC was not significant for either genetic variant in this cohort (Bongaerts et al., 2011). In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, the total alcohol intake showed a more pronounced association with CRC risk among subject carriers of the rare ADH7 C/C variant allele, with an OR of 1.80 (95% CI 1.02 to 3.17, p = 0.04) when comparing the highest alcohol intake against the lowest alcohol intake among G/C and G/G wild-type subjects (Ferrari et al., 2012). Individuals from a Chinese population with the wild-type ALDH2 G/G encoding the active acetaldehyde metabolizer subunit had higher CRC risk, independent of alcohol consumption, OR 1.79 (95% CI 1.19 to 2.69, p not reported) (Gao et al., 2008). The EPIC study reported a statistically significant association between high alcohol intake, >25 and 50 g/d in women and men, respectively, and the wild-type ALDH2 T/T genotype, for CRC, OR 1.43 (95% CI 1.06 to 1.94, p = 0.03) (Ferrari et al., 2012). DNA Repair Gene Mutations. In a Japanese population, other genetic variants such as polymorphisms found in the CYP2E1 RsaI gene and the 96-bp insertion variant were found to have different effects when ≥2 drinks of alcohol were consumed daily (Morita et al., 2009). Individuals with RsaI c1/c1 had significantly increased risk for CRC, OR 1.56 (95% CI 1.05 to 2.43, p = 0.03), while c1/c2 and c2/c2 were not significant, OR 1.29 (95% CI 0.79 to 2.11, p = 0.40) (Morita et al., 2009). Individuals that did not have 96-bp

1287

insertions were at significantly higher risk for CRC, OR 1.78 (95% CI 1.19 to 2.68, p = 0.009), than individuals with one or two 96-bp insertions, OR 0.98 (95% CI 0.59 to 1.62, p = 0.88) (Morita et al., 2009). Alcohol intake above 12 drinks per week was significantly associated with rectal cancer in men, OR 1.60 (95% CI 0.95 to 2.68, p = 0.03), and for individuals with microsatellite instability-low (MSI-L) tumors, OR 1.85 (95% CI 1.06 to 3.24, p = 0.03) (Poynter et al., 2009). Tumors that were classified as microsatellite stable and microsatellite instabilityhigh (MSI-H) were not found to be significantly associated with CRC risk when consuming alcohol (Poynter et al., 2009). One other study identified high beer intake was significantly associated with TP53 tumor mutations, OR 1.97 (95% CI 1.24 to 3.12, p = 0.02) (Slattery et al., 2010). The other tumor markers evaluated, CpG island methylator phenotype and KRAS2, were not found to be significantly associated with alcohol and CRC risk (Slattery et al., 2010). Two studies reported on XRCC1 gene polymorphisms at different allele segments, Arg194Trp, Arg280His, Arg399Gln (Gao et al., 2013; Yin et al., 2012). A significant interaction was found for homozygous carriers of 280 Arg and alcohol on CRC risk, OR 1.02 (95% CI 0.77 to 1.35) for 20 g/d, OR 2.38 (95% CI 1.51 to 3.74, p < 0.0001) (Gao et al., 2013). Mechanism of Action Protective Effects of Moderate Wine. Red wine was found to provide added benefit for reducing CRC risk in some populations; the protective effect is thought to occur due to wine’s abundant source of antioxidant compounds such as polyphenols (Kontou et al., 2012). Flavonoids, resveratrol, and proanthocyanidins are polyphenol varieties attributed to red wine (Kontou et al., 2012), which have been hypothesized to prevent or delay the onset of intestinal diseases through antioxidant activity, inflammation inhibition, and anticarcinogenic effects (Biasi et al., 2014). Some studies have concluded that resveratrol protects against cancer in all stages of carcinogenesis (Kontou et al., 2012) and has been observed to inhibit events associated with tumor initiation (Park et al., 2009). Within the context of a Mediterranean diet, alcohol consumption (Grosso et al., 2014) and especially wine consumption (Kontou et al., 2012) appeared to have the greatest protective effect for CRC risk. The health benefits found for those with greater adherence to the Mediterranean diet

KLARICH ET AL.

1288

suggested that the combination of alcohol and polyphenols produce synergistic effects with compounds found in other groups of food (Grosso et al., 2014; Kontou et al., 2012). Adverse Effects of Alcohol. High alcohol intakes, above 30 g/d, were found to have detrimental effects on CRC risk for some populations. There were numerous mechanisms cited as possible influences for the development of CRC. Alcohol has been regarded as carcinogenic to the colon and rectum through local solvent action, facilitating the absorption of its metabolite acetaldehyde, a known carcinogen, and other contaminants into the epithelial cells (Boffetta and Hashibe, 2006; Cuomo et al., 2014). Increased epithelial damage may be attributed to the microbes living in the intestinal tract, mainly the colon, due to their alcohol metabolizing capability, which contributes to acetaldehyde accumulating in the colon (Bongaerts et al., 2011; Ferrari et al., 2012; Homann et al., 2009). The breakdown of alcohol also produces reactive oxygen species and nitrogen species, which contribute to increased oxidative stress, lipid peroxidation, and DNA damage in the intestinal lumen (Boffetta and Hashibe, 2006; Gao et al., 2013; Homann et al., 2009; Yin et al., 2012). The metabolite of alcohol, acetaldehyde, causes additional damage through its ability to form stable adducts with DNA (Boffetta and Hashibe, 2006; Gao et al., 2013; Yin et al., 2012), interfere with folate metabolism to induce DNA hypomethylation (Boffetta and Hashibe, 2006; Ferrari et al., 2012; Giovannucci, 2004; Homann et al., 2009; Nan et al., 2013; Yin et al., 2012), and interfere with DNA repair function (Gao et al., 2013; Poynter et al., 2009; Yin et al., 2012). In addition, alcohol and acetaldehyde are also metabolized at different rates among individuals due to genetic variations in ADH and ALDH; the combination of certain genotypes may contribute additional CRC risk in some populations (Bongaerts et al., 2011; Cho et al., 2012; Ferrari et al., 2012; Gao et al., 2008; Homann et al., 2009; Seitz and Stickel, 2010). Similarly, the liver detoxification enzyme, cytochrome P450, may have altered induction capabilities at higher alcohol intakes, which can lead to impaired procarcinogen metabolism (Boffetta and Hashibe, 2006; Morita et al., 2009). Elevated levels of alcohol can also interfere with immune functions by inhibiting the activity of natural killer cells; thus, immune surveillance suppression may facilitate cancer metastasis (Boffetta and Hashibe, 2006; Cuomo et al., 2014).

DISCUSSION No Associated CRC Risk for Moderate Alcohol Intake Previous review articles have reported adverse effects of alcohol consumption on CRC risk (Fedirko et al., 2011; WCRF/AICR, 2007). The present review found that the detrimental effect of high alcohol intake on the incidence of CRC was consistent with previous reports (Kontou et al.,

2012; Park et al., 2009, 2010); however, the results also suggested there was no increased risk for CRC when consuming up to 30 g/d of alcohol (Bongaerts et al., 2008; Grosso et al., 2014; Kontou et al., 2012; Nan et al., 2013; Park et al., 2010; Razzak et al., 2011; Zhao et al., 2012). The discrepancies between previous reports may be due to inappropriate stratification of alcohol intakes, with moderate intakes ranging from 12.6 to 49.9 g/d alcohol (Fedirko et al., 2011). In many of the current studies, intakes >30 g/d alcohol were considered to be high intakes. It is possible that including the risk estimates from the higher intakes, pooled with the risk estimates for consumers of

Moderate Alcohol Consumption and Colorectal Cancer Risk.

Heavy alcohol drinking is a risk factor for colorectal cancer (CRC); previous studies have shown a linear dose-dependent association between alcohol i...
168KB Sizes 3 Downloads 10 Views